US4022891A
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Novel 1α,24-dihydroxycholecalciferol compositions, novel precursors thereof, and processes for preparing them
Assignee: Teijin Ltd
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Filing: 1975-06-02
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Granted: 1977-05-10
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Expires: 1995-06-02
Abstract
Abstract Novel 1α, 24-dihydroxycholecalciferol and derivatives thereof which are useful with reduced side-effects for the treatment of abnormal metabolism of calcium and phosphorus caused by liver failure, renal failure, gastrointestinal tract failure and parathyroid failure, and related bone diseases. Preparation of the novel 1α, 24-dihydroxycholecalciferol and their derivatives starts from 1α, 24-dihydroxycholesterol prepared by reacting 1α, 2α-epoxy-24-keto-cholesta-4,6-dien-3-one with an alkali metal and a proton donor in the presence of liquid ammonia or a liquid amine. Reaction of the 1α, 24-dihydroxycholesterol with an allylic brominating agent, followed by contacting with a dehydrobrominating agent, affords 1α,3β, 24-trihydroxycholesta-5,7-diene derivative, which can then be converted to 1α, 24-dihydroxycholocalciferol by ultraviolet irradiation in a organic solvent, followed by isomerization. Processes are also provided for separating 1α, 24-dihydroxycholesterol into an (S)-epimer and an (R)-epimer, and also for separating at least one of 1α, 3β, 24(S)-and 1α, 3β, 24(R)-trihydroxycholesta-5,7-dienes from trihydroxycholesta-4,6-diene.
Inventors
- 👤 Toru Takeshita
- 👤 Yoshinobu Hashimoto
- 👤 Hiroyuki Kawashima
- 👤 Sachio Ishimoto
- 👤 Nobuo Ikekawa
- 👤 Masuo Morisaki
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 13:11
CPC Classifications
C; C07; C07J; C07J9/00; A; A23; A23K; A23K20/00; A23K20/10; A23K20/174; C07J71/00; C07J71/0005; C07J71/001; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 61
Claim 1
Independent Claim
15 words
A mixture in arbitrary ratios of 1α,24(S)-dihydroxycholecalciferol and 1α,24(R)-dihydroxycholecalciferol expressed by the following formula ##STR31##
Claim 2
Dependent Claim
15 words
A mixture in arbitrary ratios of 1α,24(S)-dihydroxycholecalciferol and 1α,24(R)-dihydroxycholecalciferol expressed by the following formula ##STR31##
Claim 3
Dependent Claim
7 words
1α,24(S)-dihydroxycholecalciferol expressed by the following formula ##STR32##
Claim 4
Dependent Claim
7 words
1α,24(S)-dihydroxycholecalciferol expressed by the following formula ##STR32##
Claim 5
Dependent Claim
7 words
1α,24(R)-dihydroxycholecalciferol expressed by the following formula ##STR33##
Claim 6
Dependent Claim
7 words
1α,24(R)-dihydroxycholecalciferol expressed by the following formula ##STR33##
Claim 7
Dependent Claim
101 words
A 1α,24(S)-dihydroxycholecalciferol derivative, a 1α,24(R)-dihydroxycholecalciferol derivative, or a mixture of these in arbitrary ratios, expressed by the following formula ##STR34## wherein R 1 , R 2 and R 3 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl with the proviso that at least one of R 1 , R 2 and R 3 is said protective group.
Claim 8
Dependent Claim
101 words
A 1α,24(S)-dihydroxycholecalciferol derivative, a 1α,24(R)-dihydroxycholecalciferol derivative, or a mixture of these in arbitrary ratios, expressed by the following formula ##STR34## wherein R 1 , R 2 and R 3 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl with the proviso that at least one of R 1 , R 2 and R 3 is said protective group.
Claim 9
Dependent Claim
82 words
A mixture in arbitrary ratios of 1α,3β,24(S)-trihydroxycholesta-5,7-diene or its derivative and 1α,3β,24(R)-trihydroxycholesta-5,7-diene or its derivative, expressed by the following formula ##STR35## wherein R 1 , R 2 and R 3 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-subsituted derivatives, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 10
Dependent Claim
82 words
A mixture in arbitrary ratios of 1α,3β,24(S)-trihydroxycholesta-5,7-diene or its derivative and 1α,3β,24(R)-trihydroxycholesta-5,7-diene or its derivative, expressed by the following formula ##STR35## wherein R 1 , R 2 and R 3 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-subsituted derivatives, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 11
Dependent Claim
83 words
1α,3β,24(S)-trihydroxycholesta-5,7-diene or a derivative thereof resulting from the protection of at least one hydroxyl group thereof, expressed by the following formula ##STR36## wherein R 1 , R 2 and R 3 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivative, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 12
Dependent Claim
83 words
1α,3β,24(S)-trihydroxycholesta-5,7-diene or a derivative thereof resulting from the protection of at least one hydroxyl group thereof, expressed by the following formula ##STR36## wherein R 1 , R 2 and R 3 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivative, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 13
Dependent Claim
83 words
1α,3β,24(R)-trihydroxycholesta-5,7-diene or a derivative thereof resulting from the protection of at least one hydroxyl group thereof, expressed by the following formula ##STR37## wherein R 1 , R 2 and R 3 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 14
Dependent Claim
83 words
1α,3β,24(R)-trihydroxycholesta-5,7-diene or a derivative thereof resulting from the protection of at least one hydroxyl group thereof, expressed by the following formula ##STR37## wherein R 1 , R 2 and R 3 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 15
Dependent Claim
83 words
1α,24-dihydroxycholesterol or a derivative thereof resulting from the protection of at least one hydroxy group thereof, expressed by the following formula ##STR38## wherein R 4 , R 5 and R 6 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substitued derivatives, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 16
Dependent Claim
83 words
1α,24-dihydroxycholesterol or a derivative thereof resulting from the protection of at least one hydroxy group thereof, expressed by the following formula ##STR38## wherein R 4 , R 5 and R 6 are identical or different and represent a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substitued derivatives, tert.-butyl, benzyl, triphenyl-methyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 17
Dependent Claim
86 words
1α,24(S)-dihydroxycholesterol or a derivative thereof resulting from the protection of at least one hydroxyl group thereof, expressed by the following formula ##STR39## wherein R" 4 is a hydrogen atom or a substituted or unsubstituted benzoyl group, and R 5 is a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenylmethyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 18
Dependent Claim
86 words
1α,24(S)-dihydroxycholesterol or a derivative thereof resulting from the protection of at least one hydroxyl group thereof, expressed by the following formula ##STR39## wherein R" 4 is a hydrogen atom or a substituted or unsubstituted benzoyl group, and R 5 is a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenylmethyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 19
Dependent Claim
86 words
1α,24(R)-dihydroxycholesterol or a derivative thereof resulting from the protection of at least one hydroxyl group thereof, expressed by the following formula ##STR40## wherein R" 4 is a hydrogen atom or a substituted or unsubstituted benzoyl group and R 5 is a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benyzl, triphenylmethyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 20
Dependent Claim
86 words
1α,24(R)-dihydroxycholesterol or a derivative thereof resulting from the protection of at least one hydroxyl group thereof, expressed by the following formula ##STR40## wherein R" 4 is a hydrogen atom or a substituted or unsubstituted benzoyl group and R 5 is a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benyzl, triphenylmethyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl.
Claim 21
Dependent Claim
6 words
1α,2α-epoxy-24-ketocholesta-4,6-dien-3-one of the following formula ##STR41##
Claim 22
Dependent Claim
6 words
1α,2α-epoxy-24-ketocholesta-4,6-dien-3-one of the following formula ##STR41##
Claim 23
Dependent Claim
36 words
A process for preparing 1α,24-dihydroxycholesterol of the following formula ##STR42## which comprises reacting 1α,2α-epoxy-24-keto-cholesta-4,6-dien-3-one of the formula ##STR43## with an alkali metal and a proton donor in the presence of liquid ammonia or a liquid amine.
Claim 24
Dependent Claim
36 words
A process for preparing 1α,24-dihydroxycholesterol of the following formula ##STR42## which comprises reacting 1α,2α-epoxy-24-keto-cholesta-4,6-dien-3-one of the formula ##STR43## with an alkali metal and a proton donor in the presence of liquid ammonia or a liquid amine.
Claim 25
Dependent Claim
104 words
A process for recovering a benzoyl derivative of 1α,24(S)-dihydroxycholesterol and a benzoyl derivative of 1α,24(R)-dihydroxycholesterol, which comprises separating a benzoyl derivative of 1α,24-dihydroxycholesterol of the following formula ##STR44## wherein R" 4 is a substituted or unsubstituted benzoyl group, and R 5 is a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butly, benzyl, triphenylmethyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl, into a 1α,24(S)-epimer and a 1α,24(R)-epimer by chromatography using a carrier at least containing silicon dioxide.
Claim 26
Dependent Claim
104 words
A process for recovering a benzoyl derivative of 1α,24(S)-dihydroxycholesterol and a benzoyl derivative of 1α,24(R)-dihydroxycholesterol, which comprises separating a benzoyl derivative of 1α,24-dihydroxycholesterol of the following formula ##STR44## wherein R" 4 is a substituted or unsubstituted benzoyl group, and R 5 is a hydrogen atom or a protective group convertible to a hydrogen atom which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butly, benzyl, triphenylmethyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl, into a 1α,24(S)-epimer and a 1α,24(R)-epimer by chromatography using a carrier at least containing silicon dioxide.
Claim 27
Dependent Claim
163 words
A process for preparing at least one of a 1α,3β,24(S)-trihydroxycholesta-5,7-diene derivative and a 1α,3β,24(R)-trihydroxycholesta-5,7-diene derivative expressed by the following formula ##STR45## wherein R' 4 , R' 5 and R' 6 are identical or different, and represent a protective group convertible to a hydrogen atom without changing the structure of formula (3) which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenylmethy, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl, which comprises reacting at least one of a 1α,24(S)-dihydroxycholesterol derivative and a 1α,24(R)-dihydroxycholesterol derivative expressed by the following formula ##STR46## wherein R' 4 , R' 5 and R' 6 are the same as defined above, with an allylic brominating agent selected from the group consisting of N-bromosuccinimide, 1,3-dibromo-5,5-dimethyl hydantoin and N-bromocaprolactam in an inert organic medium, and then contacting the resulting reaction mixture with a dehydrobrominating agent selected from the group consisting of trimethyl phosphite, S-collidine and diethylaniline.
Claim 28
Dependent Claim
163 words
A process for preparing at least one of a 1α,3β,24(S)-trihydroxycholesta-5,7-diene derivative and a 1α,3β,24(R)-trihydroxycholesta-5,7-diene derivative expressed by the following formula ##STR45## wherein R' 4 , R' 5 and R' 6 are identical or different, and represent a protective group convertible to a hydrogen atom without changing the structure of formula (3) which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenylmethy, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl, which comprises reacting at least one of a 1α,24(S)-dihydroxycholesterol derivative and a 1α,24(R)-dihydroxycholesterol derivative expressed by the following formula ##STR46## wherein R' 4 , R' 5 and R' 6 are the same as defined above, with an allylic brominating agent selected from the group consisting of N-bromosuccinimide, 1,3-dibromo-5,5-dimethyl hydantoin and N-bromocaprolactam in an inert organic medium, and then contacting the resulting reaction mixture with a dehydrobrominating agent selected from the group consisting of trimethyl phosphite, S-collidine and diethylaniline.
Claim 29
Dependent Claim
66 words
A process for separating and recovering at least one of 1α,3β,24(S)- and 1α,3β,24(R)-trihydroxycholesta-5,7-diene from trihydroxycholesta-4,6-diene by a chromatographic procedure, which comprises contacting a mixture at least containing at least one of 1α,3β,24(S)- and 1α,3β,24(R)-trihydroxycholesta-5,7-diene of the followng formula ##STR47## and trihydroxycholesta-4,6-diene of the following formula ##STR48## as a solution in an inert organic solvent with a carrier containing silicon dioxide and having adsorbed thereto non-metallic silver.
Claim 30
Dependent Claim
66 words
A process for separating and recovering at least one of 1α,3β,24(S)- and 1α,3β,24(R)-trihydroxycholesta-5,7-diene from trihydroxycholesta-4,6-diene by a chromatographic procedure, which comprises contacting a mixture at least containing at least one of 1α,3β,24(S)- and 1α,3β,24(R)-trihydroxycholesta-5,7-diene of the followng formula ##STR47## and trihydroxycholesta-4,6-diene of the following formula ##STR48## as a solution in an inert organic solvent with a carrier containing silicon dioxide and having adsorbed thereto non-metallic silver.
Claim 31
Dependent Claim
212 words
A process for preparing at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferol of the followng formula ##STR49## which comprises hydrolyzing or reductively decomposing at least one of protected 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferol expressed by the following formula ##STR50## wherein R 1 , R 2 and R 3 are the same or different and represent a hydrogen atom or a protective group convertible to hydrogen which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenylmethyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl, with the proviso that at least one of R 1 , R 2 and R 3 represents a protective group convertible to a hydrogen atom, thereby to split off the protective group wherein when the protective group is the C 1 -C 12 aliphatic or aromatic carboxylic acid residue or the nitrogen-, halogen- and alkoxy-substituted derivatives thereof, the protective group is split off by hydrolyzing with an alkali solution of an alcohol or by reductively decomposing with lithium-aluminum tetrahydride; and when the protective group is the tert.-butyl, benzyl, triphenylmethyl, tetrahydropyranyl, methoxy methyl or alkyl-substituted silyl group, the protective group is split off by hydrolyzing with an acid or alkali or by reductively decomposing with lithium-aluminum tetrahydride.
Claim 32
Dependent Claim
212 words
A process for preparing at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferol of the followng formula ##STR49## which comprises hydrolyzing or reductively decomposing at least one of protected 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferol expressed by the following formula ##STR50## wherein R 1 , R 2 and R 3 are the same or different and represent a hydrogen atom or a protective group convertible to hydrogen which is selected from the group consisting of C 1 -C 12 aliphatic and aromatic carboxylic acid residues and their nitrogen-, halogen-, and alkoxy-substituted derivatives, tert.-butyl, benzyl, triphenylmethyl, tetrahydropyranyl, methoxy methyl and alkyl-substituted silyl, with the proviso that at least one of R 1 , R 2 and R 3 represents a protective group convertible to a hydrogen atom, thereby to split off the protective group wherein when the protective group is the C 1 -C 12 aliphatic or aromatic carboxylic acid residue or the nitrogen-, halogen- and alkoxy-substituted derivatives thereof, the protective group is split off by hydrolyzing with an alkali solution of an alcohol or by reductively decomposing with lithium-aluminum tetrahydride; and when the protective group is the tert.-butyl, benzyl, triphenylmethyl, tetrahydropyranyl, methoxy methyl or alkyl-substituted silyl group, the protective group is split off by hydrolyzing with an acid or alkali or by reductively decomposing with lithium-aluminum tetrahydride.
Claim 33
Dependent Claim
24 words
A pharmaceutically effective composition for warmblooded animals comprising a pharmaceutically effective amount of at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of the formula ##STR51##
Claim 34
Dependent Claim
24 words
A pharmaceutically effective composition for warmblooded animals comprising a pharmaceutically effective amount of at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of the formula ##STR51##
Claim 35
Dependent Claim
46 words
A pharmaceutical composition for warm-blooded animals according to claim 17 which is administrable orally or by intramuscular or intravenous injection, said composition comprising a pharmaceutically effective amount of at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) and a vehicle non-toxic to warm-blooded animals.
Claim 36
Dependent Claim
39 words
A pharmaceutical composition for controlling calcium metabolism of warm-blooded animals according to claim 17 which comprises a pharmaceutically effective amount of at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) and a vehicle non-toxic to warm-blooded animals.
Claim 37
Dependent Claim
36 words
A prophylactic or therapeutic pharmaceutical composition for vitamin D deficient diseases and related diseases according to claim 17, which comprises a pharmaceutically effective amount of at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a).
Claim 38
Independent Claim
35 words
A method for controlling the calcium metabolism of warm-blooded animals, which comprises administering a pharmaceutically effective amount of at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5a) ##STR52## orally, subcutaneously, intramuscularly or intravenously.
Claim 39
Independent Claim
35 words
A method for controlling the calcium metabolism of warm-blooded animals, which comprises administering a pharmaceutically effective amount of at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5a) ##STR52## orally, subcutaneously, intramuscularly or intravenously.
Claim 40
Dependent Claim
23 words
The method of claim 21 wherein the effective amount is 0.01 to 10 μg daily per kilogram body weight of the warm-blooded animal.
Claim 41
Dependent Claim
46 words
A method for preventing or treting vitamin D deficiency-induced diseases or related diseases of man according to claim 21, which comprises administering to a human a pharmaceutically effective amount of at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) orally, subcutaneously, intramuscularly or intravenously.
Claim 42
Independent Claim
50 words
A method for treating vitamin D resistant hypocalcemia and bone diseases, which comprises administering at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR53## to a patient in a disage of 0.01 to 10 μg per kilogram of the body weight daily either orally, subcutaneously, intramuscularly or intravenously.
Claim 43
Independent Claim
50 words
A method for treating vitamin D resistant hypocalcemia and bone diseases, which comprises administering at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR53## to a patient in a disage of 0.01 to 10 μg per kilogram of the body weight daily either orally, subcutaneously, intramuscularly or intravenously.
Claim 44
Dependent Claim
21 words
The method of claim 24 wherein the hypercalchemia is vitamin D dependent rickets, hypoparathyroidism, post-operative renal osteodystorophy, liver cirrhosis, or steatorrhoea.
Claim 45
Independent Claim
46 words
A method for treating osteoporosis, which comprises administering at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR54## to a patient in a dosage of 0.01 to 10 μg per kilogram of the body weight per 24 hours either orally, subcutaneously, intramuscularly or intravenously.
Claim 46
Independent Claim
46 words
A method for treating osteoporosis, which comprises administering at least one of the 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR54## to a patient in a dosage of 0.01 to 10 μg per kilogram of the body weight per 24 hours either orally, subcutaneously, intramuscularly or intravenously.
Claim 47
Independent Claim
45 words
A method for treating osteomalacia, which comprises administering at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR55## to a patient in a dosage of 0.01 to 10 μg per kilogram of the body weight per 24 hours either orally, subcutaneously, intramuscularly or intravenously.
Claim 48
Independent Claim
45 words
A method for treating osteomalacia, which comprises administering at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR55## to a patient in a dosage of 0.01 to 10 μg per kilogram of the body weight per 24 hours either orally, subcutaneously, intramuscularly or intravenously.
Claim 49
Independent Claim
46 words
A method for treating malabsorption syndrome, which comprises administering at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR56## to a patient in a dosage of 0.01 to 10 μg per kilogram of the body weight per 24 hours either orally, subcutaneously, intramuscularly or intravenously.
Claim 50
Independent Claim
46 words
A method for treating malabsorption syndrome, which comprises administering at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR56## to a patient in a dosage of 0.01 to 10 μg per kilogram of the body weight per 24 hours either orally, subcutaneously, intramuscularly or intravenously.
Claim 51
Independent Claim
26 words
A method for preventing hypocalcemia of domestic animals, which comprises administering at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR57## to a domestic animal.
Claim 52
Independent Claim
26 words
A method for preventing hypocalcemia of domestic animals, which comprises administering at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR57## to a domestic animal.
Claim 53
Independent Claim
27 words
A method for preventing the laying of soft-shelled eggs by poultry, which comprises administering at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR58## to poultry.
Claim 54
Independent Claim
27 words
A method for preventing the laying of soft-shelled eggs by poultry, which comprises administering at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR58## to poultry.
Claim 55
Dependent Claim
29 words
A feed for domestic animals and poultry comprising 0.2 to 20 g, per kilogram of the feed, of at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR59##
Claim 56
Dependent Claim
29 words
A feed for domestic animals and poultry comprising 0.2 to 20 g, per kilogram of the feed, of at least one of 1α,24(S)- and 1α,24(R)-dihydroxycholecalciferols of formula (5-a) ##STR59##
Claim 57
Dependent Claim
22 words
The method of claim 21 wherein the effective amount is from 0.04 to 0.4 mg. per kilogram of body weight, per day.
Claim 58
Dependent Claim
22 words
The method of claim 24 wherein the effective amount is from 0.04 to 0.4 mg. per kilogram of body weight per day.
Claim 59
Dependent Claim
22 words
The method of claim 26 wherein the effective amount is from 0.04 to 0.4 mg. per kilogram of body weight, per day.
Claim 60
Dependent Claim
22 words
The method of claim 27 wherein the effective amount is from 0.04 to 0.4 mg. per kilogram of body weight, per day.
Claim 61
Dependent Claim
22 words
The method of claim 28 wherein the effective amount is from 0.04 to 0.4 mg. per kilogram of body weight, per day.
References Cited (Backward Citations)
US3901928A
Cited
US3928397A
Cited
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1980-05-09 | 1980-11-08 | 1981-05-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-05-09 | 1984-11-08 | 1985-05-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-05-09 | 1988-11-08 | 1989-05-10 | $7700.00 | Window Closed / Lapsed |